Journal article

Direct tumor lysis by NK cells uses a Ras-independent mitogen-activated protein kinase signal pathway

S Wei, DL Gilvary, BC Corliss, S Sebti, JZ Sun, DB Straus, PJ Leibson, JA Trapani, AD Hamilton, MJ Weber, JY Djeu

The Journal of Immunology | AMER ASSOC IMMUNOLOGISTS | Published : 2000


Destruction of tumor cells is a key function of lymphocytes, but the molecular processes driving it are unclear. Analysis of signal molecules indicated that mitogen-activated protein kinase (MAPK)/extracellular regulated kinase 2 critically controlled lytic function in human NK cells. We now have evidence to indicate that target ligation triggers a Ras-independent MAPK pathway that is required for lysis of the ligated tumor cell. Target engagement caused NK cells to rapidly activate MAPK within 5 min, and PD098059 effectively blocked both MAPK activation and tumoricidal function in NK cells. Target engagement also rapidly activated Ras, detected as active Ras-GTP bound to GST-Raf-RBD, a GST ..

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